Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, USA.
Mol Cell Biochem. 2010 Oct;343(1-2):217-22. doi: 10.1007/s11010-010-0516-4. Epub 2010 Jun 13.
Endothelial dysfunction is an early manifestation of atherosclerosis caused in part by oxidized LDL (oxLDL). Since vitamin C, or ascorbic acid, prevents several aspects of endothelial dysfunction, the effects of oxLDL on oxidative stress and regulation of the ascorbate transporter, SVCT2, were studied in cultured EA.hy926 endothelial cells. Cells cultured for 18 h with 0.2 mg/ml oxLDL showed increased lipid peroxidation that was prevented by a single addition of 0.25 mM ascorbate at the beginning of the incubation. This protection caused a decrease in intracellular ascorbate, but no change in the cell content of GSH. In the absence of ascorbate, oxLDL increased SVCT2 protein and function during 18 h in culture. Although culture of the cells with ascorbate did not affect SVCT2 protein expression, the oxLDL-induced increase in SVCT2 protein expression was prevented by ascorbate. These results suggest that up-regulation of endothelial cell SVCT2 expression and function may help to maintain intracellular ascorbate during oxLDL-induced oxidative stress, and that ascorbate in turn can prevent this effect.
内皮功能障碍是动脉粥样硬化的早期表现，部分是由氧化型 LDL（oxLDL）引起的。由于维生素 C（抗坏血酸）可预防内皮功能障碍的多个方面，因此研究了 oxLDL 对培养的 EA.hy926 内皮细胞的氧化应激和抗坏血酸盐转运体 SVCT2 调节的影响。用 0.2 mg/ml oxLDL 培养细胞 18 h 后，细胞内脂质过氧化增加，而在孵育开始时单次添加 0.25 mM 抗坏血酸可预防这种增加。这种保护作用导致细胞内抗坏血酸减少，但细胞内 GSH 含量没有变化。在没有抗坏血酸的情况下，oxLDL 在培养的 18 h 内增加了 SVCT2 蛋白和功能。尽管用抗坏血酸培养细胞不会影响 SVCT2 蛋白表达，但抗坏血酸可预防 oxLDL 诱导的 SVCT2 蛋白表达增加。这些结果表明，内皮细胞 SVCT2 表达和功能的上调可能有助于在 oxLDL 诱导的氧化应激期间维持细胞内抗坏血酸，而抗坏血酸反过来又可以预防这种作用。
